Digestive System

https://digitalcommons.imsa.edu/hd_graphic_novels/1030/thumbnail.jp

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Measuring the Response of Nevomelanocytes to MBEH, 4-TBP, and 8-DPAT

Congenital nevi are pigmented moles present at birth that have a 2 to 20-fold increase in the chance of developing melanoma. In the past, melanoma has been treated using bleaching agents to give patients a more even skin tone which they may prefer. Bleaching seems to have a cytotoxicity towards melanocytes and not keratinocytes meaning it provides an effective solution. More specifically, the phenols in experimentation are MBEH, 4-TBP, and 8-DPAT. Since it is similar to the amino acid tyrosine, monobenzyl ether of hydroquinone (MBEH) is able to be converted into a highly reactive quinone which can act in a melanosomal cell to restrict melanocyte expression. Additionally, 4-tertiary butyl phenol (4-TBP) has been proven to induce apoptosis in the targeted regions and 8-DPAT has been used to reduce the cytotoxicity of the specific region to reduce chances of nevus cells becoming tumorigenic, ensuring that stem cell like cells do not differentiate. Thus, bleaching allows for a non-intrusive form of removing the congenital nevi and preventing future melanoma that can help in situations of extensive lesions where options such as skin grafts are not a viable choice. The experimentation aims to test and characterize the effect of these phenols on nevomelanocytes

Schizophrenia

What is Schizophrenia? •Schizophrenia is a neural disorder characterized by a difficulty to distinguish reality from fantasy[1] Symptoms[5] Delusions – “These are false beliefs that are not based in reality” Hallucinations – “These usually involve seeing or hearing things that don\u27t exist. Yet for the person with schizophrenia, they have the full force and impact of a normal experience. ” Disorganized thinking – Consists of Impaired speaking ability meaning that questions may not be completely answered or complete thoughts may not be expressed Extremely disorganized motor behavior – “Behavior isn\u27t focused on a goal, so it\u27s hard to do tasks. Behavior can include resistance to instructions, inappropriate or bizarre posture, a complete lack of response, or useless and excessive movement.”https://digitalcommons.imsa.edu/mcb_mh_posters/1009/thumbnail.jp

Looking at GD3 as an immunotherapeutic target to treat benign TSC Tumors

Tuberous sclerosis complex (TSC), is a genetic disorder presenting with benign tumors which can pose severe health problems including altered organ function. A method to combat TSC might be to target ganglioside D3 (GD3) which is overexpressed in TSC tissues. Chimeric antigen receptor transduced T cells (CAR T-cells) specific to GD3 were injected into a mouse model of TSC to measure whether CAR T-cells mediate a robust immune response to tumors. The project incorporates using TSC2 heterozygote mice that develop TSC tumors in the liver and kidneys after about 9 months. After CAR T cell infusion, the liver and tissue were preserved and sectioned for immunofluorescence staining to characterize immune responses and GD3 expression. CD4 and CD8 T cell staining marked the immune infiltration. GD3 expression in the TSC-diseased mice was found to be significantly higher (

The Effects of Probiotics through Maternal Administration in the Gut Development of Pups

Probiotics have been found to be useful in reducing necrotizing enterocolitis in preterm infants. However, many times these infants are unable to absorb the probiotics due to the poor ability for some microbes to finish colonizing the gut. Early microbial colonization has shown the potential to improve the immune system in infants and therefore is crucial to the short- and long-term well-being of the infant. A mouse model was used to understand how treating the damps with the probiotics could affect the gut microbiota and the small intestinal development of the pup. Markers such as enteroendocrine cells, goblet cells, and Paneth cells throughout the villi and crypts of the sectioned tissues through typical immunofluorescent and enzymatic stainings were used to describe levels of the immune responses and stages of development in the small intestine. The stainings indicated that the probiotics facilitated the development of these cells and promoted the integrity of the immune system and inflammatory response towards threats. These results indicate that probiotics may be administered through the damp and may be a safer method to reduce necrotizing enterocolitis in preterm infant